The robust regeneration potential of fetal tissue suggests that developmental biology may help guide strategies for tissue regeneration in adults. Decreases in regenerative capacity post-utero and with increasing age are likely due to multiple factors, however one important contributor may be changes in the availability and functionality of stem cells responsible for mounting a reparative response to injury. The overall objectives of this Bioengineering Research Partnership are to characterize and quantitatively compare the relative regenerative capacity of stem cells isolated from two distinct stages of human development (fetal and adult) and assess the effectiveness of different strategies for delivering stem cells for bone regeneration. The central hypothesis governing this research is that augmenting the number of viable stem cells at the injury site and promoting their reparative phenotype will significantly enhance functional repair of bone defects and spine fusion in a developmental stage dependent manner. To test this hypothesis, the multidisciplinary team will integrate stem cell biology with tissue engineering principles and well-established, quantitative test bed models. The approach will employ customized gene array analysis to elucidate differential gene regulation pathways of stem cells derived from amniotic fluid and adult bone marrow at baseline and during osteogenic differentiation. Composite scaffold and nanofiber mesh biomaterials technologies will be evaluated for their ability to effectively deliver stem cells for segmental defect repair and spine fusion. Finally, a novel biomimetic coating technology will be investigated as a means to program delivered stem cells towards the osteogenic phenotype. The proposed research is unique in that there has been very little to no previous research on quantitatively comparing the regenerative capacity of different stem cell sources, particularly from distinct developmental stages. The expected outcome of these studies is the identification of an effective stem cell source and delivery protocol that may be rapidly translated into new therapeutic options for patients lacking adequate endogenous cell repair mechanisms. PUBLIC HEALTH RELEVANCE: Injured or degenerated musculoskeletal tissues are the most common cause of long-term pain and disability world-wide, motivating efforts to develop new tissue regenerative therapies. Using novel cell delivery approaches, this project will quantitatively compare the regenerative capacity of two non-embryonic stem cell sources from different developmental stages (fetal and adult) in the clinically relevant settings of large bone defects and spine fusion.